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Objective: To examine on-court core body temperature (TC) and sweat loss, as well as pre- and post-play hydration status, in elite adolescent tennis players during a national championships event in a hot climate. Methods: Eight healthy, fit, young male tennis players (mean (SD) age 13.9 (0.9) years; mass 56.0(10.7) kg; height 169.2 (14.7) cm) were evaluated during first-round singles competition at the National Boys' 14s Junior Championships in the heat (wet-bulb globe temperature (WBGT) 29.6 (0.4) °C). Five of those same players were also evaluated during a same-day doubles match (WBGT 31.3 (0.5) °C). Results: During doubles (4.37 (0.35) h after singles), pre-play urine specific gravity (USG) (1.025 (0.002); p=0.06) and total sweat loss (1.9 (0.2) litres; p=0.10) tended to be higher before and during doubles, respectively, compared to singles. However, percentage change in body mass (-0.5 (0.3) %) tended to be comparatively less (p=0.08), even though the doubles matches were generally longer (106.6 (11.2) vs 78.8 (10.9) min; p=0.09) and the degree minutes total was greater (p=0.04). TC increased (p<0.001) during singles and remained elevated, even after 10 mm following the end of play. Notably, pre-play (singles) USG was strongly associated (p=0.005) with the players' final TC (38.7 (0.3) °C) recorded at the end of singles play. Conclusion: Junior tennis players who begin a match not well hydrated could have progressively increasing thermal strain and a greater risk for exertional heat illness as the match advances. [ABSTRACT FROM AUTHOR]

Aim: To determine if expression of colonic tryptophan hydroxylase-2 (TPH2), a surrogate marker of neuronal 5-hydroxytryptamine, is altered in Hirschsprung's-associated enterocolitis., Methods: Entire resected colonic specimens were collected at the time of pull-through operation in children with Hirschsprung's disease (HSCR, n = 12). Five of these patients had a history of pre-operative Hirschsprung's-associated enterocolitis (HAEC). Controls were collected at colostomy closure in children with anorectal malformation (n = 10). The distribution of expression of TPH2 was evaluated using immunofluorescence and confocal microscopy. Protein expression of TPH2 was quantified using western blot analysis in the deep smooth muscle layers., Results: TPH2 was co-expressed in nitrergic and cholinergic ganglia in the myenteric and submucosal plexuses in ganglionic colon in HSCR and healthy controls. Co-expression was also seen in submucosal interstitial cells of Cajal and PDGFRα(+) cells. The density of TPH2 immuno-positive fibers decreased incrementally from ganglionic bowel to transition zone bowel to aganglionic bowel in the myenteric plexus. Expression of TPH2 was reduced in ganglionic bowel in those affected by pre-operative HAEC compared to those without HAEC and healthy controls. However, expression of TPH2 was similar or high compared to controls in the colons of children who had undergone diverting colostomy for medically refractory HAEC., Conclusion: Altered TPH2 expression in colonic serotonergic nerves of patients with HSCR complicated by HAEC may contribute to intestinal secretory and motor disturbances, including recurrent HAEC.

Background: The Accreditation Council for Graduate Medical Education (ACGME) duty-hour requirements prompted program directors to rethink the organizational structure of their residency programs. Many surgical educators have expressed concerns that duty-hour restrictions would negatively affect quality of resident education. This article summarizes evaluation research results collected to study the impact of our reengineered residency program designed to preserve important educational activities while meeting duty-hour accreditation requirements., Study Design: The traditional residency structure was redesigned to include a mixture of apprenticeship, small team, and night-float models. Impact evaluation data were collected using operative case logs, standardized test scores, quality assurance data, resident perception surveys, a faculty survey, and process evaluation measures., Results: PGY1s and PGY2s enjoyed a substantial increase in operative cases. Operative cases increased overall and no resident has failed to meet ACGME volume or distribution requirements. American Board of Surgery In-Training Examination performance improved for PGY1s and PGY2s. Patient outcomes measures, including monthly mortality and number of and charges for admissions, showed no changes. Anonymously completed rotation evaluation forms showed stable or improved resident perceptions of case load, continuity, operating room teaching, appropriate level of faculty involvement and supervision, encouragement to attend conferences, and general assessment of the learning environment. A quality-of-life survey completed by residents before and after implementation of the new program structure showed substantial improvements. Faculty surveys showed perceived increases in work hours and job dissatisfaction. New physician assistant and nurse positions directly attributed to duty-hour restrictions amounted to about 0.2 full-time equivalent per resident., Conclusions: Duty-hour restrictions produce new challenges and might require additional resources but need not cause a deterioration of surgical residents' educational experience.

Background: To evaluate the antitumor activity, toxicities, and pharmacokinetics (PK) of DX-8951f administered as a 30-min infusion daily for 5 days every 3 weeks in patients with fluorouracil-resistant metastatic colorectal carcinoma., Patients and Methods: Sixteen patients were enrolled. All had metastatic colorectal carcinoma resistant to or progressing after chemotherapy containing 5-fluorouracil and no prior chemotherapy with camptothecin derivatives. DX-8951f was administered until disease progression or unacceptable toxicity. Responses were assessed after every two courses., Results: Fifteen patients were evaluable. Fifty-one courses of therapy were delivered (median 2). Responses were one minor response, six stable disease, and eight progressive disease. The principal adverse event was neutropenia, with grade 3 and 4 toxicities in three and eight patients, respectively. Non-hematologic toxicities were mild to moderate; the most common were fatigue, nausea, and diarrhea. Plasma concentrations of DX-8951 were well described using a linear two-compartment PK model. There was no evidence of nonlinearity in the elimination of PK or auto-inhibition or induction of DX-8951 clearance over the 5 days of administration., Conclusions: DX-8951f at this dose and schedule had no significant activity in this patient population. The toxicity profile, mainly hematologic, was consistent with previous reports. The clearance and volume of distribution were not different from those previously reported.

Purpose: The purpose of this study was to assess the feasibility of administering exatecan, a water-soluble, potent camptothecin analogue, as a protracted 21-day continuous i.v. infusion (CIVI). The study also sought to determine the maximum tolerated dose (MTD) of exatecan on a 21-day CIVI schedule, characterize its pharmacokinetic behavior, and seek preliminary evidence of anticancer activity., Experimental Design: Exatecan dose-schedule development was performed in two stages using the modified Continual Reassessment Method and single patient cohorts. First, patients with advanced solid malignancies were treated with exatecan (0.15 mg/m(2)/day) as a CIVI for 5 days, and the duration of the CIVI was incrementally increased from 5 to 21 days. In the second stage of the study, the dose was incrementally increased to derive a tolerable dose of exatecan administered as 21-day CIVI. The MTD was defined for both minimally pretreated (MP) and heavily pretreated (HP) patients as the highest dose level at which the incidence of dose-limiting toxicity does not exceed 20%., Results: Thirty-one patients were treated with 100 courses of exatecan at 6 dose-schedule levels. The incidence of the principal dose-limiting toxicities, neutropenia and thrombocytopenia, was unacceptably high at exatecan doses exceeding 0.15 mg/m(2)/day as a 21-day CIVI, which was determined to be the MTD for both MP and HP patients. The pharmacokinetics of exatecan were dose-proportional, and mean [coefficient of variation (percentage) steady-state concentration (plasma concentration at steady-state)] values ranged from 6.88 (80.6) to 19.41 (74.2) ng/ml at exatecan dose levels ranging from 0.15 to 0.30 mg/m(2)/day, which are similar to IC(50) values against human tumor cell lines treated for shorter periods. Mean pharamacokinetic parameters for total exatecan derived from a compartmental model included clearance and volume of distribution values of 1.39 (86.9) liters/h/m(2) and 39.66 (197.4) liters, respectively. Two HP patients with non-small cell lung and unknown primary carcinomas had partial responses, and objective evidence of anticancer activity and clinical benefit were noted in several other individuals., Conclusions: The administration of exatecan as a 21-day CIVI at doses as high as 0.15 mg/m(2)/day is safe and feasible for both MP and HP patients. The characteristics of the myelosuppressive effects of exatecan on this schedule, the paucity of severe nonhematological toxicities, and documented anticancer activity in several drug-refractory malignancies warrant further evaluation of the merits of administering exatecan by either a CIVI or alternate drug delivery systems to achieve protracted systemic exposure.